imaging of the breast in young women - 108 harley street · imaging of the breast in young women...

Imaging of the Breast in Young Women

William Teh

Northwick Park Hospital

North London Breast Screening Centre

The London Breast Clinic Symposium

6th May 2010

Two main rationale:

Breasts relatively radiosensitive under the age of 35

In absence of risk factors, probability of malignancy increases with age

Imaging of the Breast By Age

Below 12 years: Rarely required – most commonly occasional breast buds in toddlers and pre-pubertal breast changes

12 – 16: Ultrasound

16 – 25: Ultrasound: most common solid lesions are fibroadenomas. If needle biopsy required usually FNA

25-35: Ultrasound. Core biopsy preferred

35 and above: Mammography and US. Core biopsy if abnormality detected.

Imaging of the Breast By Age

Full field digital mammography superior in multi-centre trials for cancer detection in:

Pre/peri-menopausal women

Women with dense breasts / HRT

Women < 50

Not indicated unless symptomatic in under 40s

DMIST 2005

Mammography in pre-menopausal

women

> 75% mammographic density => 4-5x risk

Women with decrease of breast density over 6 years – 28% lower risk

?higher aromatase levels (converts androgens to oestrogens)

16% higher risk of cancer recurrence

American Association for Cancer Research 2010

Cancer 2009

San Antonio 2008

Mammographic density and risk of

breast cancer

Tomosynthesis

Digital contrast examinations

Quantification of risk using mammographic density

Mammographic developments

Not as good as mammography in fatty breasts, adipose breasts or large breasts.

Limited application in young women with benign breast change

Shown to be slightly more effective than mammography but significantly inferior to MRI in women with family history

High risk studies: mammography + US – 52% sensitivity vs mammography + MRI – 92.7% sensitivity

ACRIN6666 study shows high false positive detection (only 8.8% biopsies were cancers)

Ultrasound of the Breast:

Alternative to screening mammograms?

Most sensitive method for detection of breast cancer

Contrast enhanced – vascularity of tumours

Multiple applications –

Implant assessment

Scar vs. cancer recurrence

Further evaluation of proven malignancy: local staging & multi-focality (NICE 2009)

Detection of occult breast cancer in axillary lymph node metastasis

Screening high-risk pre-menopausal women

Monitoring neo-adjuvant chemotherapy

MRI: Form… and function

North West London Hospitals NHS

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MRI and Silicone Implants

Meta-analyses 1099 implants over 7 years

Median life-span 16.4 years; 79.1% intact

at 10 years, falling to 48.7% by 15 years

sensitivity specificity

Mammo 28.4 92.9

US 59 76.8

MRI 78.1 80

Goodman CM et al. Annals of Pl Surg 1998;41(6):577-585


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MRI:

Implants


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Pre-operative MRIIncreasingly used to assess extent of biopsy proven cancer, multi-focality/centricity, dense breasts, invasive lobular carcinoma

Surgical treatment changed in 13% -34%

Multi-focality / multicentricity 16%

Contralateral malignancy 3.1% (ACRIN 6667 study NEJM 2007)

Lehman et al NEJM 2007

Martinez-Cecilia et al ECCO 2008

Krishnan M et al, Antonella et al, Lehman C et al ARRS 2008

Houssammi et al, J Clin Oncol 2008


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Pre-operative MRIOffer magnetic resonance imaging (MRI) of the breast to

patients with invasive breast cancer:

if discrepancy regarding extent of disease from clinical examination, mammography and ultrasound assessment for planning treatment

if breast density precludes accurate mammographic assessment

to assess the tumour size if breast conserving surgery is being considered for invasive lobular cancer.

NICE 2009


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Pre-operative MRIMay delay definitive surgery due to delays in MRIs and investigations of false positives (41 days vs 27 days)

Unnecessary investigations and biopsies (40-50%)

Risk influencing unnecessary mastectomies (12.5-33%)

No evidence of impact on local recurrence rate or mortality benefit as yet

Sandberg A et al, Krishnan M et al. ARRS 2008


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Pre-operative MRI8.1% conversion from wide local excision to mastectomy due

to true positive findings

1.1% conversion from wide local excision to mastectomy due

to false positive findings

3.0% conversion from wide local excision to wider/additional

excision due to true positive findings;

4.4% conversion from wide local excision to wider/additional

excision due to false positive findings.

Over-treatment can be decreased by using second look

US/MRI guided biopsy

Houssami 2008

Eusoma 2010


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Pre-operative MRI: EUSOMA

(2010)Patients with invasive lobular cancer

Patients at high risk of breast cancer

Patients <60 with discrepancy of >1cm between mammographic findings and US findings

Patients eligible for partial breast irradiation

Patients must be aware of risks and benefits

Delay should not be > 1 month

MRI biopsy/localisation should be accessible


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MRI in axillary metastases

McMahon K, Medoro L, Kennedy D Australas Radiol. 2005

Sensitivity 85.7% accuracy 86.7%

78% confirmed histologically

55% suitable for conservative surgery

Morris et al – 9/12 (75%) detected; 8/12 (66.7%)

suitable for conservation

Koh et al 2007 – 10/12 (83%) detected; 2/12

remain disease free at 39 and 44 months

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22McMahon+K%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22Medoro+L%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22Kennedy+D%22%5BAuthor%5D


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38 yo right metastatic axillary nodes – dense breasts cysts.


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MRI for neoadjuvant

chemotherapyMonitoring response to neoadjuvant chemotherapy

Baseline, mid-cycle, completion of chemo

Assessment of response may be possible after one or two cycles

Particularly useful to assess if conservative surgery feasible

BUT does not exclude presence of residual disease – eg Belli et al 2007 – 90.5% sensitivity, 100% specificity, 91.3% accuracy in detecting residual disease


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10% breast cancers run in families (only 2%

identified mutations)

Young women who had radiotherapy for

lymphoma

MRI improves breast cancer detection even

when other tests normal (2X more cancers

detected)

MRI in high-risk premenopausal

women


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Mammography & MRI screening

guidelines

UK NICE May 2004 / October 2006

American Cancer Society Guidelines Aug 2007

NICE Breast Cancer Management 2009

Eusoma 2010


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NICE guidance: High risk10-year risk of 8% aged 30–39 & 10-year risk

of 12% aged 40–49 years:

2 close relatives diagnosed with average age < 30*



A genetic test required to determine a 10-year risk ≥20% in women 40–49.

*All relatives must be on the same side of the family and one must be a mother or sister of the woman.


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NICE guidance: High risk

BRCA1/2 – aged 30-49

TP53 – aged 20+

.50% risk of carrying mutation in gene

tested family or untested/inconclusive

tested family with 60% risk of

BRCA1/TP53

In England, 2,500/49.8 million

population


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Surveillance in high-risk

premenopausal womenInformed consent – pros and cons including

false positive/negatives

Protocols

Counselling

Genetic testing

Surveillance audited and according to

NHSBSP standards


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Mammography in high-risk

premenopausal women

According to NHSBSP standards

Higher sensitivity for DCIS (Kriege 2004)

DCIS more common in BRCA2

Should be digital mammography


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Mammography in high-risk

premenopausal womenEvidence of benefits in 40-49

No evidence of benefits in 30-39

Mammo for 30-39 ‘only as part of a approved

research study/audited service’ and ‘

individualised strategies for exceptional cases,

such as BRCA1, BRCA2 or TP53and women

with equivalent high breast cancer risk.

Not to occur in < 30s

>50s: NHSBSP


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Mamm US MRI

Kriege 2004 (Rotterdam)

MARIBS 2005 (UK)

Warner 2004 (Toronto)

Kuhl 2005

Lehman 2007

HIBCRIT 2007

Sensitivity %

51/1909 (2.7%)

35/649 (5.4%)

22/236 (9.3%)

43/529 (8.1%)

6/171 (3.5%)

28/278 (4.3%)

33.3

40

36

32.6

33.3

59%

-

-

33

40

17

65(+

1)

79.5

77 (97% both)

77 (95% all)

90.7 (93% all)

100

94 (+6)

Kriege 2004 (Rotterdam)

MARIBS 2005 (UK)

Warner 2004 (Toronto)

Kuhl 2005

Lehman 2007

Specificity % 95

93

99.8

96.8

99

-

-

96

89.8

82 (77% all)

95.4

97.2 (96.1%

all)

95

EVA Multi centre trial (ASCO 2008)

687 high risk women 2002-2005 (27 cancers overall

incidence 16.1/1000)

FFDM, US, MRI

FFDM only – 9 cancers

FFDM + US – 4 additional cancers

FFDM + MRI – all cancers (2 DCIS on FFDM only)

US + MRI – no additional cancers

US vs MRI in high risk


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NICE guidance (summary):

Age Risk Mammo MRI

20+ TP53 No Yes

30-39 TP53, BRCA1/2

10yr risk > 8%

(Yes) Yes

40-49 TP53 (50% risk)

BRCA1/2 (50%

risk)

10 yr risk > 20%

10yr risk > 12%

and ‘dense’ breasts

Yes

Yes

Yes

Yes

Yes

Yes

Yes


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Breast Surveillance In Young Women Post

Supradiaphragmatic Irradiation (SDI) for

Hodgkin’s DiseaseSDI < 17 y.o. – screen from age 25

SDI 17-35: screening to begin 8 years after completion of treatment.

EAG 2003

Age (years) Recommended surveillance

< 25 No imaging

25-29 Annual MRI (if contraindicated annual US)

30-50 Baseline mammograms. ± MRI (breast desnity)

>50 NHS BSP


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Risk Groups - questions

Other groups:

?follow-up for treated breast cancer

? Atypia

? Dense breasts

What about > 50s?

What about MRI in moderate risk groups?


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High risk screening to be aligned with

NHSBSP

Investment include Digital Mammography

MRI screening QA criteria requires critical

volume and radiological expertise (already

required for Hodgkin’s)

UK Cancer Reform Strategy

Dec 2007:


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Minimum technical standards

Double reading (minimum 5,000 mammo

and 100 MRI/year)

MRI vacuum biopsy – minimum 100 non-

MR and 12 MR-vacuum biopsies / year

Standards low – currently only 1 centre in

UK exceeds 12 MR vacuum biopsies / year!

Draft NHSBSP MRI Screening:


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Progress so far:

Only 6/82 NHSBSP units have gone digital

Only 1 NHSBSP service in London fully digital

Only 1 MRI unit in UK undertakes more than 12 MRI guided biopsies a year


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Summary

Imaging (US and mammograms) straified by age

(US < 35)

Digital mammography best in < 50s / pre/peri-

menopausal

MRI used effectively in high risk screening,

optimised by MDT for pre-operative staging, neo-

adjuvant chemotherapy, implant complication and

occult axillary metastases

Research questions for other sub-groups

imaging of the breast in young women - 108 harley street · imaging of the breast in young women...

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